Formation of Lipopolysaccharides

Lipopolysaccharides or LPS are essential for Gram-negative bacteria, providing structural support and aiding immune evasion.

LPS consists of lipid A, a core oligosaccharide, and the O antigen.

Lipid A biosynthesis begins in the cytoplasm with uridine diphosphate N-acetylglucosamine, which undergoes enzymatic acylation.

It forms a tetra-acylated intermediate that undergoes sequential modifications as additional fatty acids are added.

Further acylation produces a hexa-acylated lipid A; next, glycosyltransferases sequentially attach the core oligosaccharide to lipid A.

This Lipid A-core complex is then transported across the inner membrane by the MsbA transporter.

Meanwhile, the O antigen is assembled on a carrier lipid in the cytoplasm and flipped to the periplasm.

In the periplasm, O antigen units are polymerized and ligated to the lipid A-core, forming the complete LPS.

Finally, the lipopolysaccharide transport system moves the LPS across the periplasm and incorporates it into the outer membrane, strengthening bacterial defense.